Late‐onset Focal Dermal Elastosis—dermatoscopic and ultrasonographic assessment of this rare entity and literature review

Dear Editor, Late Onset Focal Dermal Elastosis (LOFDE) is a rare, acquired cutaneous entity. Clinically, it usually presents as multiple, small, flat, white to pale yellow papules located on the sides of the neck and flexural areas.1–2 The lesions might be asymptomatic or pruritic and generally occur in the elderly skin. Mainly women are affected.3 In several reports regarding LOFDE, only a single case was described in a male patient.4 The histopathological hallmark of LOFDE is the accumulation of the structurally normal elastic tissue in the mid and deep reticular dermis forming conglomerates pushing up collagen bundles.3 Although LOFDEmight clinically resemble pseudoxanthoma elasticum (PXE), their histopathological features differ, and no systemic disorders have been found in this condition. Other differential diagnoses include elastofibroma, papillary dermal elastolysis, nevus elasticus and Buschke-Ollendorff syndrome.1 The pathogenesis of this entity is not known; however, some theories have been proposed. Since there are no clues of solar elastosis in histopathology, ageing not related to sun damage might have an impact on the appearance of the skin lesions.3

The loss of an age-related growth-regulating gene control mechanism leading to the overproduction of structurally healthy tissue has been described in this entity. 5On the other hand, overexpression of elastin has also been proposed. 4The changes in this entity are irreversible and the treatment is targeted to relief sometimes concomitant pruritus. 3r patient is a 57-year-old woman presenting with multiple, asymptomatic, unilateral yellowish papules located predominantly on the skin of the right lower extremity and groin.Single lesions were noticed on the right part of the abdomen (Figure 1A,B).The accentuation of the papules was marked after skin stretching.Furthermore, the lesions did not cross the middle line of the body.They appeared about 3-4 years prior to the visit, although the patient was not sure of the duration since she noticed them once they had been spread.
On dermatoscopy (DermLite DL5, 10x magnification) white globules, corresponding to the accumulation of the connective tissue, presumably elastic tissue pushing collagen bundles were noticeable (Figure 2A).They were also visible as bright, blue globules in the Ultraviolet-Induced Fluorescence Dermatoscopy (Figure 2B).In high  frequency ultrasound (HFUS, DermaScan Cortex C, 20 MHz) hypoechogenic round-shaped lesion with poorly demarcated borders covered by hyperechogenic entrance echo were observed (Figure 2C).A 4 mm punch skin biopsy was taken, and histopathology revealed normal epidermis covered with lamellar keratin.The mid and deep reticular dermis was dense with thickened fibrillar bundles corresponding with the papule (Figure 3A).In orcein staining pink bundles were detected as structurally normal, increased in amount, dispersed between collagen bundles elastic fibers (Figure 3B).No fragmentation, phagocytosis, histiocytic or inflammatory response was noticeable.The pathological findings were consistent with focal dermal elastosis, and in correlation with clinical presentation in the 57-yo woman as late-onset FDE.
To our knowledge, this is one of the very few described cases of late-onset focal dermal elastosis, and the first one analyzed with non-invasive skin imaging techniques such as dermatoscopy and highfrequency ultrasound.A review of the available LOFDE cases in the literature is presented in Table 1.
Considering the fact that the pathogenesis of LOFDE has not been determined, it might be an underreported entity due to its peculiar clinical presentation.LOFDE papules clinically strongly mimic pseudoxanthoma elasticum (PXE) as well as the fibrotic phase of guttate morphea.In dermatoscopy, PXE reveals yellow-to-white clods on a reddish or whitish background, along with linear, irregular vessels, 6,7 whereas in HFUS, oval, homogeneous, hypoechogenic areas in the  Yes dermis due to fat lobules herniations into atrophic skin, in for example, dermal striae. 9Histology with elastic tissue stain will emphasize the distinctive elastic fibers arrangement in LOFDE, since elastic fibers are normal and increased in amount, while in dermal striae elastic fibers are curled and clumped at the edge of the lesion and reduced in the deep dermis enabling fat tissue hernia formation. 9Additionally, the two entities present contrasting clinical features.Thickening of the skin, both clinically and in HFUS, can be observed in other rare entities, such as acromegaly, 10 or morphea. 11The former phenomenon, in addition to the obvious clinical diversity, is due to increased fibroblasts density and their activation in the reticular dermis.Therefore, the thicker skin in acromegaly differs from focal dermal elastosis in HFUS since the dermis is uniformly thickened without hypoechogenic areas.
Wang et al. 10 reported a different dermoscopic image compared to the one we observed in LOFDE.Subsequently, in the fibrotic phase of morphea, the so-called "fibrotic beams" (white clouds), which correspond to sclerotic collagen bundles in the mid and deep dermis, can be seen in dermatoscopy. 11,12HFUS on the other hand, shows hyperechogenic dermis, acoustic attenuation of the dermis, and the unclear boundary between the dermis and the subcutaneous fat. 11 conclusion, taking into account the clinical picture of LOFDE, it seems that both HFUS and dermoscopy may be helpful in the diag-nosis of this rare entity, but in doubtful cases, histologic examination and histochemical staining will determine the cause of decreased hyperechogenicity of collagen fibers.

CONFLICT OF INTEREST STATEMENT
No potential conflict of interest was reported by the authors.
mid and deep dermis, undulating skin surface with regular epidermis, and normoechogenic, interpapular dermis can be seen.According to Guérin-Moreau et al., PXE skin is primarily hypoechogenic. 8In the case of LOFDE, dermatoscopy presents white globules (better attenuated in the Ultraviolet-Induced Reflectance Dermatoscopy) on an erythemateous background, while HFUS shows the separation of the collagen fibers in the reticular dermis as hypoechoic areas (corresponding to the accumulation of the elastic fibers as histology confirmed), similarly as HFUS has shown low-reflection echoes in the deep F I G U R E 3 (A) H&E image of the lesion biopsy presents preserved epidermis and reticular dermis with densely packed collagen bundles, 100x; (B) orcein staining highlights the focal increase of structurally normal elastic fibers dispersed between collagen bundles, 100x.
Cases of late-onset focal dermal elastosis available from the literature.